Long-term effects of immunostimulation on synaptic plasticity and neurodegeneration
[thesis]
Marianna Beyer, Universitätsbibliothek Braunschweig, Martin Korte
2016
The innate immunity provides rapid and important protection against invading pathogens and obtains clearance of pathogen-associated as well as host-derived danger-associated material. Microglia and astrocytes induce an inflammatory response by production of pro-inflammatory cytokines in the brain, termed neuroinflammation. Neuroinflammation is part of the pathogenesis of neurodegenerative diseases and prolonged innate immune activation has been identified as risk factor for Alzheimer´s disease.
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... In this thesis, the long-term influences of a systemic immune activation on neuronal architecture, function and learning behavior of mice were investigated. Different inflammatory components as well as the influence of age were examined. Additionally the APP/PS1 mouse model of Alzheimer´s disease was taken to determine changes in neurodegeneration upon immune stimulation. The presented data provide evidence for an age-dependent vulnerability towards an immune stimulation with lipopolysaccharide (LPS) of Salmonella enterica serovar typhimurium (S.typhimurium) as well as with peptidoglycan (PGN) and lipoteichoic acid (LTA) of Staphylococcus aureus. Aged mice exhibit decreased dendritic complexity and spine density of hippocampal and cortical excitatory neurons. Moreover, the long-term potentiation (LTP) as enduring enhanced synaptic transmission reflecting the cellular correlate of learning, and the formation of spatial memory, was impaired in aged wildtype mice. Moreover, aged mice showed a higher microglia activation and further activation upon LPS stimulation. The treatment with LPS of Escherichia coli (E.coli) did not show these deleterious effects. However, in aged APP/PS1 mice, both E.coli and S.typhimurium LPS resulted in reduction of dendritic branches and spine density of hippocampal and cortical excitatory neurons. Moreover, synaptic plasticity was inhibited with both kinds of LPS and upon PGN/LTA treatment. Interestingly, also adult APP/PS1 mice exhibited detrimental effects on neuronal morphology upon systemic im [...]
doi:10.24355/dbbs.084-201606131142-0
fatcat:gfip4jkxkfet5ecvzwahizcnum